Infection of birds with oncogenic preparations of reticuloendotheliosis virus (REV) results in the rapid induction of a "null" suppressor cell population which inhibits the proliferation of thymus-derived (T) lymphocytes. The suppression of the proliferation response of cells from uninfected birds is cytostatic and does not involve a diffusable factor or virus. Contact between a trypsin-sensitive surface protein on the suppressor cell with the target cells is required for the inhibition of the proliferative response. Oncogenic preparations of REV contain two viruses: a replication-defective transforming virus (REV), and a nontransforming helper virus (designated reticuloendotheliosis-associated virus, (REV-A)) which apparently induces the suppressor cells. REV-transformed, nonvirus producing cells will be used to directly define the contribution of REV tumor cells to the immunosuppression. EFforts will be initiated to define the mechanism by which suppressor cells are generated in birds infected by REV-A. One possible mechanism is suggested by the rapidity with which the suppressor cell population is generated (as early as 3 days after infection) and the observation from lytically infected cells could induce the suppressor cells in vivo. We will also define whether suppressor cells generated by REV infection are directed against REV tumor cells or against cells transformed by genetically unrelated viruses. We also propose to determine whether a correlation exists between the lack of suppressor cells and the resistance of older chickens to virulent REV infection. We will also determine whether severe and rapid immunosuppression develops in chickens infected with other genetically unrelated avian acute leukemia viruses in order to determine if rapid immunosuppression accounts for the difference in time of onset between the lymphoproliferative diseases induced by chronic and acute leukemia viruses. The study of the effect of these suppressor cells on immune responsiveness as it relates to the development of reticuloendotheliosis may provide a model for the understanding of the subversive effect of viral oncogenesis on immune function.